Prognostic Relevance of Transforming Growth Factor-β Receptor Expression and Signaling in Glioblastoma, Isocitrate Dehydrogenase-Wildtype. Issue 3 (22nd February 2022)

• Record Type: Journal Article
• Authors: Togni, Claudio; Rom, Emanuel; Burghardt, Isabel; Roth, Patrick; Rushing, Elisabeth J; Weller, Michael; Gramatzki, Dorothee
• Is Part Of: Journal of neuropathology and experimental neurology. Volume 81:Issue 3(2022)
• Page Start: 225
• Page End: 235
• Publication Date: 2022-02-22
• Subjects: ALK -- Glioblastoma -- Id -- Survival -- TGF-β -- TGFβRII; Neurology -- Diseases -- Periodicals; Neurology -- Diseases -- Physiopathology -- Periodicals; 616.8047
• DOI: 10.1093/jnen/nlac007
• Languages: English
• ISSNs: 0022-3069

Abstract

Abstract: The transforming growth factor (TGF)-β signaling pathway has been recognized as a major factor in promoting the aggressive behavior of glioblastoma, isocitrate dehydrogenase-wildtype. However, there is little knowledge about the expression of TGF-β receptors in glioblastoma. Here, we studied the expression patterns of TGF-β receptor II (TGFβRII), type I receptors activin receptor-like kinase (ALK)-5, and ALK-1, as well as of the transcriptional regulators inhibitor of differentiation (Id) 2, Id3, and Id4 in human glioblastoma. The expression of TGFβRII, ALK-5, and ALK-1 varied greatly, with TGFβRII and ALK-5 being the most abundant and ALK-1 being the least expressed receptor. None of the 3 receptors was preferentially expressed by tumor vasculature as opposed to the tumor bulk, indicating tumor bulk-governed mechanisms of TGF-β signaling with regard to glioblastoma-associated angiogenesis. A positive correlation was found between ALK-1 and Id2, suggesting that Id2, broadly expressed in the tumor cells, is a downstream target of this receptor-dependent pathway. Furthermore, there was a trend for high expression of ALK-5 or Id2 to be associated with inferior overall survival. Hence, we propose that ALK-5 may be used for patient stratification in future anti-TGF-β treatment trials and that Id2 might be a potential target for anti-TGF-β interventions.